Quantifying the Uncertainty of Spontaneous Ca2+ Oscillations in Astrocytes: Particulars of Alzheimer's Disease

The quantification of spontaneous calcium (Ca2+) oscillations (SCOs) in astrocytes presents a challenge because of the large irregularities in the amplitudes, durations, and initiation times of the underlying events. In this article, we use a stochastic context to account for such SCO variability, which is based on previous models for cellular Ca2+ signaling. First, we found that passive Ca2+ influx from the extracellular space determine the basal concentration of this ion in the cytosol. Second, we demonstrated the feasibility of estimating both the inositol 1,4,5-trisphosphate (IP3) production levels and the average number of IP3 receptor channels in the somatic clusters from epifluorescent Ca2+ imaging through the combination of a filtering strategy and a maximum-likelihood criterion. We estimated these two biophysical parameters using data from wild-type adult mice and age-matched transgenic mice overexpressing the 695-amino-acid isoform of human Alzheimer beta-amyloid precursor protein. We found that, together with an increase in the passive Ca2+ influx, a significant reduction in the sensitivity of G protein-coupled receptors might lie beneath the abnormalities in the astrocytic Ca2+ signaling, as was observed in rodent models of Alzheimer's disease. This study provides new, to our knowledge, indices for a quantitative analysis of SCOs in normal and pathological astrocytes.